tbuckley/cabot-search huggingface dataset:
Exploring expression levels of HER2, HER3, MET, Claudin18.2, and MUC16 across 16 cancer types using an artificial intelligence-powered immunohistochemistry analyzer.
Authors: Seunghwan Shin, Soo Ick Cho, Sangjoon Choi, Taebum Lee, Seulki Kim, Wonkyung Jung, Mohammad Mostafavi, Biagio Brattoli, Jeongun Ryu, Seonwook Park, Sergio Pereira, Ken Nesmith, Jiyoung Park, Melody SeungHui Seo, Huijeong Kim, Seokhwi Kim, Chan-Young Ock
Journal: Journal of Clinical Oncology (2023)

3135 Background: Quantifying tumor-associated antigen (TAA) expression levels on tumor cells (TC) from immunohistochemistry (IHC) stained slides has been widely used to predict response to novel anti-tumor agents. However, obtaining the precise quantification of TAA expression levels from various cancer types is still challenging. To quantify five targets of interest, we applied an artificial intelligence (AI)-powered analyzer to 16 cancer types. Methods: AI-powered whole slide image (WSI) analyzers were developed using IHC positive or negative tumor cells (TC) from PD-L1 22C3 pharmDx and HER2 4B5 datasets, annotated by pathologists. The universal model was trained by IHC-positive or negative TCs from all datasets, while the second model was trained by the intensity of positive (from 1+ to 3+) or negative TCs from the HER2 dataset. Both AI models were applied to the pan-cancer tissue microarray dataset (n = 1,370) with MUC16, CLDN18.2, MET, HER3, and HER2 IHC staining, respectively. The expression levels of those TAAs were calculated with tumor proportion score (TPS) or ASCO/CAP scoring criteria for HER2 in 16 cancer types including biliary tract, breast, colorectum, esophagus, head and neck, kidney, liver, lung, ovary, bladder, pancreas, prostate, stomach, thyroid, cervical, and endometrial cancer. Results: Based on the TPS of 1% or more, the positivity of MUC16 and CLDN18.2 were most frequently observed in ovary (51.6%) and kidney (24.2%), respectively, and MET and HER3 in colorectum (63.8%; 40.5%). The five most highly expressed tumors and their frequency of TPS≥1% are shown. HER2 3+ tumor cells were most highly expressed in the breast, followed by the bladder. Conclusions: This study describes the TAA expression levels in various tumors using an AI-powered IHC analyzer. This method could be useful for exploring target cancer types and predicting response to novel TAA targeted agents. [Table: see text]
Efficacy and safety of penpulimab-containing regimens for advanced malignant solid tumors that have failed immunotherapy: A real-world study.
Authors: Juying Zhou, Chao Xu, Lu Zhang, Chenying Ma
Journal: Journal of Clinical Oncology (2023)

e14700 Background: Immuno-checkpoint inhibitors (ICI) have shown good anti-tumor efficacy and survival benefits in a variety of solid tumors, such lung cancer, gastric cancer, esophageal cancer, head and neck squamous cell carcinoma (HNSCC). ICI have rewritten the guidelines for multiple tumor types. However, there are still a large number of patients who are ineffective or initially effective after use ICI, and subsequently develop ICI resistance. For these patients, how we choose further treatment is currently uncertain clinically. Some studies suggest that even if the treatment of PD - (L) 1 is ineffective or progresses, it can still bring a certain degree of benefit to re-challenge with other target ICI. This study was to evaluate the efficacy and safety of the patients with advanced malignant solid tumors with the regimen of penpulimab. Methods: This is a non-interventive registration study. Eligible participants must be ≥ 18 years old and have proven malignant tumors that are ineffective, fail for immunotherapy and have no other standard treatment. Patients were treated with penpulimab alone or in combination with chemotherapy or anti-angiogenic agents until progression or unacceptable toxicity. The primary endpoint is objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: Form Sep 2021 to Feb 2023, 28 patients (median age 59.5 years, male 71.4%）were recruited, including 9 pts with NSCLC, 5 pts with HNSCC, 4 pts with Nasopharyngeal carcinoma (NPC), 3 pts with esophageal cancer and 7 with other tumor types. Among all, 1 achieved confirmed PR, 21 achieved SD, the ORR was 3.6% (1/28) and the DCR was 78.6% (22/28). The median treatment duration was 9 months. Among the 9 pts with NSCLC, the median treatment duration was 5.6 months and the DCR was 77.8%. Treatment-related adverse events (TRAEs) of grade 3 were observed in 5 (17.9%) of the 28 patients. The most common TRAEs were decreased lymphocyte count (50%, 14/28), anemia (50%, 14/28), hypoalbuminemia (39.3%, 11/28), hyponatremia (25%, 7/28) and hypercholesterolemia (25%, 7/28). Conclusions: Penpulimab-containing regimens for advanced malignant solid tumors that have failed ICI have shown significant efficacy and a favorable safety profile.
Atypical response patterns in Chinese patients with cancer with immune checkpoint blockade.
Authors: Yu Cui, Yaping Guan, Xinyue Han, Hong Xie, Yingcui Chen, Weiwei Nie, Jun Wang
Journal: Journal of Clinical Oncology (2023)

e14631 Background: As specific patterns of progression, atypical responses, including pseudoprogression (PsPD) and dissociated response (DR), have been recently described. The purpose of the present study was to evaluate the frequency and prognosis of PsPD and DR in Chinese cancer patients treated with immune checkpoint inhibitors. Methods: We retrospectively reviewed patients with advanced cancer who received PD-1/PD-L1 inhibitor alone or combination therapy in a single center between December 2019 and January 2022. We evaluated all measurable lesions in each organ to identify PsPD and DR independently of RECIST 1.1. PsPD was defined as RECIST-defined progression followed by stabilization or decrease at the next imaging, and DR as concomitant decrease in some lesions and increase in others or emerging new lesions at a same timepoint. Progression‐free survival (PFS) and overall survival (OS) was compared between patients with atypical responses and those with true response (CR/PR) or nonresponse (SD/PD) using Cox proportional hazards models. Results: The present study included 178 patients aged 18-81 years (median: 63 years). The overall response rate was 18.5%. PsPD and DR were observed in 12 (6.7%) and 7 (3.9%) patients, respectively, and were not associated with any patient’s baseline characteristics. Median PFS (10.9 vs. 5.3 months; p=0.041) and OS (24.1 vs. 13.2 months; p=0.010) was significantly longer in patients with atypical response versus nonresponse, but shorter versus true responses (PFS: 10.9 vs. 35.4 months; p=0.009; OS: 24.1 vs. NR months; p=0.047). Patients with DR had a longer median PFS (10.1 vs. 1.5 months; p&lt;0.0001) and OS (23.9 vs. 5.6 months; p=0.0001) than those with true PD. All patients with PsPD or DR were administrated with continuing ICIs. Among patients who experienced an initial progression (excluding patients with PsPD and DR), the continuing ICIs treatment cohort (n=20) still had a significantly longer median OS (7.5 vs. 3.1 months; p=0.004) than discontinuing ICIs treatment cohort (n=11). Conclusions: PsPD and DR are uncommon patterns of disease progression. Patients with DR exhibited a relatively favorable clinical outcome. Prognosis or biomarkers are needed to identify early patients with atypical responses who will benefit from immunotherapy.
ENGOT-EN20/GOG-3083/xport-EC-042: A phase 3, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with P53 wild-type, advanced or recurrent endometrial carcinoma.
Authors: Ignace Vergote, Mansoor R. Mirza, Robert L. Coleman, Jose Alejandro Perez-Fidalgo, Bradley J. Monk, Giorgio Valabrega, Brian M. Slomovitz, Toon Van Gorp, Kathleen N. Moore, Jalid Sehouli, David Cibula, Tally Levy, Gerasimos Aravantinos, Kai Li, Pratheek Kalyanapu, Vicky Makker
Journal: Journal of Clinical Oncology (2023)

TPS5627 Background: Patients (pts) with first-line metastatic or recurrent endometrial cancer (EC) have a poor prognosis. Selinexor is an oral XPO1 inhibitor, which leads to nuclear accumulation of tumor suppressor proteins, including p53. Selinexor is FDA-approved for use in multiple myeloma and diffuse large B-cell lymphoma, and has shown clinical activity in previously treated, advanced EC. Molecular characterization of EC is critical in directing treatment for advanced and recurrent disease. Of the EC molecular subtypes, TP53 wild type (wt) tumors represent 50% of advanced and recurrent tumors. A recent phase 3 study in maintenance after chemotherapy found that, despite the primary endpoint (PFS) not reaching statistical significance, prolonged PFS of oral once-weekly selinexor versus placebo (13.7 months and 3.7 months, respectively) was observed in a prespecified exploratory subgroup analysis of patients with advanced or recurrent TP53wt EC. Methods: XPORT-EC-042 (NCT05611931) is a Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of selinexor as maintenance therapy in pts with TP53wt advanced or recurrent EC, who have achieved a partial response or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after completing at least 12 weeks of platinum combination chemotherapy ±immunotherapy for primary stage IV or recurrent disease. Eligible pts must be ≥18 years of age, have histologically confirmed EC, and TP53 wt disease based on NGS sequencing assessed by Foundation Medicine. Pts will be randomized 1:1 with either selinexor 60 mg or placebo once weekly in 28-day cycles until progressive disease, toxicity, or 3 years if in complete response. A total of 220 pts will be enrolled at sites across the United States, Canada, Europe, and Israel. The primary objective is to compare PFS in pts treated with selinexor compared to placebo based on RECIST v1.1 criteria as assessed by the Investigator. Key secondary objective is overall survival. Other secondary objectives are safety, time to first subsequent therapy, time to second subsequent therapy, time from randomization until the second progression event (PFS2), and PFS by a blinded independent central review. Patient enrollment is ongoing. Clinical trial information: NCT05611931 .
Safety and tolerability of HLX07 combined with chemotherapy in patients with advanced solid tumors.
Authors: Qun Li, Ye Guo, Junli Xue, Xiaoxiao Ge, Fengjuan Lin, Liqiong Xue, Wei Zhao, Wenbo Tang, Chen Hu, Hongyan Ni, Jing Li, Qingyu Wang, Jun Zhu, Jin Li
Journal: Journal of Clinical Oncology (2023)

e15001 Background: HLX07 is a novel humanized anti-EGFR monoclonal antibody. This study aimed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of HLX07 combined with different chemotherapy regimens (chemo-regimens) in patients with advanced solid tumors. Methods: This was a single-center, open-label, dose-escalation phase 1b/2 study. Three fixed-dose chemo-regimens were given together with HLX07: 1) gemcitabine 1000 mg/m 2 (on Days 1 and 8) and cisplatin 75 mg/m 2 (on Day 1) in 3-week cycles for 4–6 cycles; 2) paclitaxel 80 mg/m 2 and carboplatin AUC = 2 (both on Days 1, 8, and 15) in 3-week cycles for 4–6 cycles; and 3) mFOLFOX6 (on Day 1) in 2-week cycles for 6–12 cycles. Patients with metastatic or recurrent advanced solid tumors suitable to be treated with the above chemo-regimens were given HLX07 IV at escalating doses (400, 600, or 800 mg, QW) combined with chemotherapies following BOIN design. The primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary endpoints included safety and preliminary efficacy. Results: As of August 28, 2022, 56 patients were enrolled; 21 received HLX07 with gemcitabine and cisplatin, 21 received HLX07 with paclitaxel and carboplatin (n = 3 for HLX07 400 and 600 mg, n = 15 for HLX07 800 mg for each chemo-regimen), and 14 received HLX07 with mFOLFOX6 (n = 3 for HLX07 400 and 600 mg, n = 8 for HLX07 800 mg). No DLT related to HLX07 was reported. The MTD was not reached. A summary of treatment-emergent adverse events (TEAEs) in each group is shown in Table 1. All patients experienced TEAEs. Grade ≥3 TEAEs were reported by 17 (81.0%), 20 (95.2%), and 12 (85.7%) patients in each chemo-regimen group, respectively. Only 1 (33.3%) patient in the HLX07 400 mg plus paclitaxel and carboplatin group experienced TEAE leading to death (upper gastrointestinal hemorrhage, possibly unrelated to study drugs). Conclusions: HLX07 was safe and well tolerated when combined with chemotherapy in patients with advance solid tumors. Clinical trial information: NCT03577704 . [Table: see text]
Phase 1 study of LB1410, a bivalent TIM-3/PD-1 bispecific antibody, in patients with advanced solid tumors or lymphoma.
Authors: Jiajian Liu
Journal: Journal of Clinical Oncology (2023)

TPS2663 Background: Cancer immunotherapies targeting PD-1 or PD-L1 have been proven effective in causing durable antitumor immune responses with less toxicity in many types of tumors. However, the response rate of anti-PD-1/PD-L1 treatments is far from satisfactory and most patients show primary or acquired resistance to the treatments. Tim-3, one of the next generation of immune checkpoint targets, co-expressed on exhausted T cells with PD-1. It is also expressed by innate immune populations, including NK and DC. Dual blocking PD-1 and Tim-3 not only on T cells but also on DC, NK cells may achieve better clinical benefit. LB1410 is a recombinant humanized anti-PD-1/TIM-3 bispecific antibody (BsAb) developed by L&amp;L Biopharma Co., Ltd. for the patients who are resistant to or refractory from PD-1/PD-L1 treatments. It blocked the immune checkpoint PD-1 and TIM-3-mediated immunosuppressive signal pathways simultaneously, showed better T/DC cell activity and in vivo anti-tumor efficacy compared to Tim-3 and PD-1 antibody combination in preclinical studies. Methods: This is a FIH, multicenter, non-randomized, open label, phase 1 study of LB1410 in Participants With Advanced Solid Tumor or Lymphoma（Keyplus-001）. The planned sample size is approximately 100 patients in two parts: part 1 dose escalation will evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D), and Part 2 dose expansion will further characterize the safety profile and preliminary tumor response in several cohorts including NSCLC, CRC, EC etc. Enrollment criteria include adults with life expectancy of &gt; 3 months, ECOG performance status 0-1，histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies or lymphoma for which standard treatment fails, or no standard treatment is available, or standard treatment is not applicable at this stage. Exclusion criteria include pregnancy, lactation, or breastfeeding, ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments. The primary endpoints are incidence of dose limiting toxicities and adverse events, MTD, and recommended phase 2 dose. Secondary objectives will evaluate PK parameters, preliminary antitumor activity, and immunogenicity of LB1410. Besides, the pharmacodynamics (PD) biomarkers related to LB1410 treatment, clinical activity will be explored. This clinical trial is in progress; cohorts 1 to 5 in dose escalation part have been completed. Clinical trial information: NCT05357651 .
Real-world treatment sequencing and outcomes for patients with advanced renal cell carcinoma treated with cabozantinib after first-line checkpoint inhibitor-based combination therapy: Results from the CARINA study.
Authors: Paul D. Nathan, Jennifer Allison, Natalie Charnley, Richard Griffiths, Agnieszka Michael, Kathryn Moore, Anand Sharma, Bernadett Szabados, Balaji Venugopal, Jamshed Ali, Valérie Perrot, Áine Prendergast, Bhupinder Klair, James Larkin
Journal: Journal of Clinical Oncology (2023)

e16512 Background: Real-world data are required to guide the optimal sequencing of therapies for advanced renal cell carcinoma (aRCC) when first-line (1L) checkpoint inhibitor (CPI)-based combinations are used. CARINA is a retrospective, non-interventional study of treatment sequencing and outcomes in patients with aRCC who progressed to second-line (2L) treatment after 1L CPI-based combination therapy. Methods: Electronic prescribing records and hospital medical records from nine participating UK specialist centers were reviewed to identify patients (aged ≥ 18 years) with a diagnosis of aRCC who received 2L therapy after 1L CPI-based combination therapy in line with UK National Health Service funding policy. The primary objective was to describe the treatment pathways of patients with aRCC who received 1L CPI-based combination and subsequent therapy. Secondary objectives included descriptive analysis of: duration of treatment (DoT), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Here we report a descriptive analysis of outcomes for subgroups who received 2L cabozantinib or other 2L therapies. Results: Between April 2015 and June 2022, data were collected from 281 patients (163 patients received 2L cabozantinib and 118 received other 2L therapies after 1L CPI-based therapy). Overall, mean (standard deviation [SD]) age at aRCC diagnosis was 59.4 (10.1) years, 76.5% were male and 87.5% had clear-cell aRCC (including those with a clear-cell component). In the 2L cabozantinib and other 2L therapies subgroups, the most common 1L regimens were ipilimumab + nivolumab (79.1% and 60.2%, respectively), axitinib + avelumab (9.8% and 22.0%) and pembrolizumab + axitinib (9.8% and 9.3%). Outcomes of 2L treatment for the 2L cabozantinib and other 2L therapies subgroups are shown in the Table. Conclusions: Among patients with aRCC who progressed to 2L treatment after 1L CPI-based therapy, the most common 1L therapies were ipilimumab + nivolumab followed by axitinib + avelumab. DoT and ORR were numerically better with 2L cabozantinib than with other 2L therapies, demonstrating the antitumor effect of 2L cabozantinib after 1L CPI-based therapy. Clinical trial information: NCT04957160 . [Table: see text]
The relationship between a priori defined prognostic risk groups and and overall survival (OS) in men with metastatic hormone sensitive prostate cancer (mHSPC).
Authors: Susan Halabi, Siyuan S Guo, Akash Roy, Larysa Rydzewska, Peter Godolphin, Maha H. A. Hussain, Catherine Tangen, Ian Thompson, Wanling Xie, Michael Anthony Carducci, Matthew Raymond Smith, Michael J. Morris, Gwenaelle Gravis, David P. Dearnaley, Paul Verhagen, Takayuki Goto, Nicholas D. James, Mahesh Parmar, Marc E. Buyse, Christopher Sweeney
Journal: Journal of Clinical Oncology (2023)

5073 Background: Prior analyses have shown that men who present with high volume (HV) disease and de novo metastases have shorter OS compared with other mHSPC subgroups. The objective of this analysis was to determine the prognostic relationship between a-priori defined 4-prognostic groups and OS in men with mHSPC and in a subset of trials in patients treated with androgen deprivation therapy (ADT) +docetaxel. This hypothesis was investigated by the STOPCAP M1 collaborators. Methods: We obtained individual patient data (IPD) from 13 randomized trials comparing treatment regimens (ADT or ADT + docetaxel in the control or research arms) in mHSPC. OS was defined as the time between date of randomization and date of death/or last follow-up. Patients (pts) were classified into 4 mutually exclusive groups. Poor prognostic risk-group was defined as HV (presence of visceral metastases, and/or &gt; 4 bone metastases or presence of bone metastases beyond pelvic or vertebral bones) plus synchronous diagnosis (SYN); whereas intermediate risk groups were patients with HV and metachronous (MET; intermediate A) or low volume plus SYN (intermediate B); and lastly good risk group had LV plus MET. The proportional hazards model was used to estimate the hazard ratio (HR) and assess the prognostic significance of risk groups in predicting OS adjusting for treatment. Results: Of 6041 pts included in this analysis, 60% (3622 pts) had died. Median follow-up time=5-years. Overall 11%, 8%, 47% and 34% were in the good, intermediate A, intermediate B and poor risk groups, respectively and for trials including docetaxel (n=2627 pts) 9%, 5%, 39% and 47% respectively. HRs for risk groups are shown in the table. Conclusions: Differences in OS across the risk groups were observed. Further work is needed to investigate if more precise prognostic groups can be defined such as better characterization of patients' groupings of extent of bone metastases and visceral metastases. Clinical trial information: NCT00309985 ; NCT00268476 ; NCT00104715 ; NCT00079001 ; NCT00002651 ; NCT00685646 . [Table: see text]
Safety, tolerability, and pharmacokinetics of HLX26 (an anti-LAG3 antibody) in patients with advanced or metastatic solid tumors or lymphomas.
Authors: Rujiao Liu, Jian Zhang, Yang Chen, Shuiping Gao, Chen Hu, Liang Zhou, Hua Li, Wenying Kang, Jun Zhu
Journal: Journal of Clinical Oncology (2023)

e14671 Background: HLX26 is a novel humanized anti-LAG3 monoclonal antibody. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of HLX26 in patients with advanced or metastatic solid tumors or lymphomas. Methods: This was a first-in-class, multicenter, open-label, dose-escalation phase 1 study. Patients with histologically or cytologically confirmed advanced solid tumors or lymphomas who had failed or were not suitable for standard therapies were enrolled and received HLX26 at five dose levels (60, 150, 300, 500, or 800 mg, Q3W) intravenously. This study followed accelerated titration combined with a “3+3” design. HLX26 was given until disease progression with no clinical benefit, 2 years of treatment, experiencing intolerable toxicity, withdrawal of consent, or death, whichever occurred first. The primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) within DLT observation period, which was 3 weeks after the first dose of HLX26. Secondary endpoints included safety, pharmacokinetic and pharmacodynamic characteristics, preliminary efficacy, immunogenicity, and potential biomarker explorations of HLX26. Results: As of December 22, 2022, 12 patients with stage IV breast (n = 10, 83.3%) or rectum (n = 2, 16.7%) solid tumors were enrolled and received HLX26 at 60 mg (n = 1), 150 mg (n = 1), 300 mg (n = 3), 500 mg (n = 3), or 800 mg (n = 4). The mean age was 57.5 (range 31–73) years. No DLT was reported and the MTD was not determined as of yet. Eleven (91.7%) patients experienced treatment-emergent adverse events (TEAEs), most commonly hypercholesterolemia (41.7%), hypertriglyceridemia (25.0%), and hyperuricemia (25.0%). Most TEAEs were grade 1 (n = 8, 66.7%) and 2 (n = 2, 16.7%). Conclusions: In summary, no new safety signals were observed from 60 mg to 800 mg of HLX26. HLX26 was safe and well tolerated in patients with advanced or metastatic solid tumors. Clinical trial information: NCT05078593 .